Mechanism of C‑3\nAcyl Neighboring Group Participation\nin Mannuronic Acid Glycosyl Donors

One of the main challenges\nin oligosaccharide synthesis\nis the\nstereoselective introduction of the glycosidic bond. In order to understand\nand control glycosylation reactions, thorough mechanistic studies\nare required. Reaction intermediates found by NMR spectroscopy often\ncannot explain the glycosylation’s stereochemical outcome.\nHence, reactions may proceed through low-abundance reaction intermediates\nthat are difficult to detect, according to a Curtin–Hammett\nscenario. We have previously observed that manno-type sugars can engage\nin C-3 acyl neighboring group participation. Herein, we report the\ndetection of glycosyl dioxanium ions that result from C-3 neighboring\ngroup participation in mannuronic acid donors. Using a suite of exchange\nNMR techniques, we were able to dissect the kinetics of the conformational\nring-flip that precedes C-3 acyl participation and the participation\nevent itself in various manno-type sugars. Hence, this study provides\na complete picture of mannosyl dioxanium ion formation.